Histoplasma Flashcards
Is yeast or hyphae virulent?
yeast
Histo looks like TB why?
- causes lung granulomas which can turn into calcified nodules
How do biologics do?
Inhibit TNFalpha to supress immune system
What does RYP1 stand for?
Required for Yeast Phase 1
What do RYP1 do?
allows 25C hyphae to turn into 37C yeast
How did they find RYP1?
- screen for mutants unable to grow as yeast at 37C
- OR use chemical that blocks transition to yeast
How does histo survive in phagolysosome?
somehow keeps pH neutral which prevents activation of lysosomal enzymes
How does histo survive in phagolysosome?
somehow keeps pH neutral which prevents activation of lysosomal enzymes
What PRRs do histo bind to?
- Complement receptors
- most important to have CD18 which is the constant region
How did they find histo virulence factors?
- transcription microarray showed expression of each gene in a single experiment
- query how much red, green, and yellow on plate
- look for red and green outliers
- yellow = housekeeping genes
What does CBP1 stand for?
Calcium Binding Protein 1
What do CBP1 do?
kill macrophage
Which PRR is extra important to histo?
CR3 because that allows histo into macrophage
What PRRs does histo try and hide from?
- TLRs
- Dectin1
- MR
How did they test if alpha glucans where important and what did it show?
- made by Alpha Glucan Synthase 1
- remove AGS1 or block via iRNA
- AGS1- had much lower fungal burden
What do alpha glucans do for histo?
mask beta glucans from Dectin1
What does ENG1 stand for?
Extracellular endo-beta-glucanase 1
What do ENG1 do?
hydrolyzes beta glucans that peak through alpha glucan coating
How did they find ENG1?
proteomics based identification of candidate secreted protein factors
What does SOD stand for?
SuperOxide Dismutase
What SOD is secreted and what do it do?
SOD3 protects against ROS
What does Cat stand for?
Catalase
Which Cat is secreted and what do it do?
CatB protects from ROS
What do siderophores do?
steal sequestered iron
What do siderophores do?
steal sequestered iron
Why do PMN- hosts generally not get histo?
they’re not exposed because they’re in the hospital
Are T cells required to fight histo?
yes because they activate macrophages
What do RNS do to histo?
kill
What do surfactant proteins do to histo?
directly kill yeasts
Are surfactant proteins sufficient?
yes
